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Journal of Virology, February 2005, p. 2042-2049, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2042-2049.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Interactions between Natural Killer Cells and Antibody Fc Result in Enhanced Antibody Neutralization of Human Immunodeficiency Virus Type 1

Department of Medicine, Division of Infectious Diseases, University of California, Irvine, School of Medicine, Irvine, California¹

Received 19 March 2004/ Accepted 30 September 2004

Antibodies can prevent lentivirus infections in animals and may play a role in controlling viral burden in established infection. In preventing and particularly in controlling infection, antibodies likely function in the presence of large quantities of virus. In this study, we explored the mechanisms by which antibodies neutralize large inocula of human immunodeficiency virus type 1 (HIV-1) on different target cells. Immunoglobulin G (IgG) from HIV-infected patients was tested for neutralizing activity against primary R5 strains of HIV-1 at inocula ranging from 100 to 20,000 50% tissue culture infective doses. At all virus inocula, inhibition by antibody was enhanced when target cells for virus growth were monocyte-depleted, peripheral blood mononuclear cells (PBMCs) rather than CD4⁺ lymphocytes. However, enhanced inhibition on PBMCs was greatest with larger amounts of virus. Depleting PBMCs of natural killer (NK) cells, which express Fc receptors for IgG (FcRs), abrogated the enhanced antibody inhibition, whereas adding NK cells to CD4⁺ lymphocytes restored inhibition. There was no enhanced inhibition on PBMCs when F(ab')₂ was used. Further experiments demonstrated that the release of ß-chemokines, most likely through FcR triggering of NK cells, contributed modestly to the antiviral activity of antibody on PBMCs and that antibody-coated virus adsorbed to uninfected cells provided a target for NK cell-mediated inhibition of HIV-1. These results indicate that Fc-FcR interactions enhance the ability of antibody to neutralize HIV-1. Since FcR-bearing cells are always present in vivo, FcR-mediated antibody function may play a role in the ability of antibody to control lentivirus infection.

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